Functional maps of protein complexes from quantitative genetic interaction data.
Functional maps of protein complexes from quantitative genetic interaction data.
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DOI：
10.1371/journal.pcbi.1000065
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发表时间：
2008-04-18
影响因子：
4.3
通讯作者：
Ideker T
中科院分区：
文献类型：
--
作者：
Bandyopadhyay S;Kelley R;Krogan NJ;Ideker T
最近，一些先进的筛选技术已经允许全面量化基因对之间的遗传相互作用的加重和减轻。与此同时，TAP-MS研究（串联亲和纯化，然后进行质谱分析）已成功地鉴定了物理蛋白质相互作用，这些相互作用可指示参与相同分子复合物的蛋白质。在这里，我们提出了一种方法，通过整合定量遗传相互作用和TAP-MS数据来联合学习蛋白质复合物及其功能关系。使用3个独立的基准数据集，我们证明了这种方法在识别功能相关蛋白质对方面比以前的方法准确率高出50%以上。应用于参与酵母染色体组织的基因，确定了91个多聚体复合物的功能图谱，其中许多是新的或通过添加新亚基而得到了实质性扩展。有趣的是，我们发现富集了加剧遗传相互作用的复合物（即，合成致死性）更可能包含必需基因，将这些相互作用中的每一个与潜在机制联系起来。这些结果表明，大规模的遗传和物理相互作用的数据在映射通路的结构和功能的重要性。生物学家目前正在产生大量的数据集中在物理和遗传蛋白质相互作用。物理相互作用决定了细胞的结构，即分子之间的直接关联如何构成蛋白质复合物，而遗传相互作用则通过基因之间的因果关系来定义功能关系。这两种类型的相互作用都可以指示共享的蛋白质功能;然而，这两种类型的相互作用通常是不重叠的，使得它们的解释变得困难。沿着这些路线，已经注意到遗传相互作用通常发生在相同蛋白质复合物的成员之间以及功能相关的复合物之间。在这里，我们提出了一个综合框架，结合了两种类型的相互作用，以生成蛋白质复合物的大型地图，以及突出相关复合物之间的连接。以自动化方式快速整合这两种类型的数据的能力可以加速蛋白质复合物新成员的发现，以及识别功能相关的细胞组分。
Recently, a number of advanced screening technologies have allowed for the comprehensive quantification of aggravating and alleviating genetic interactions among gene pairs. In parallel, TAP-MS studies (tandem affinity purification followed by mass spectroscopy) have been successful at identifying physical protein interactions that can indicate proteins participating in the same molecular complex. Here, we propose a method for the joint learning of protein complexes and their functional relationships by integration of quantitative genetic interactions and TAP-MS data. Using 3 independent benchmark datasets, we demonstrate that this method is >50% more accurate at identifying functionally related protein pairs than previous approaches. Application to genes involved in yeast chromosome organization identifies a functional map of 91 multimeric complexes, a number of which are novel or have been substantially expanded by addition of new subunits. Interestingly, we find that complexes that are enriched for aggravating genetic interactions (i.e., synthetic lethality) are more likely to contain essential genes, linking each of these interactions to an underlying mechanism. These results demonstrate the importance of both large-scale genetic and physical interaction data in mapping pathway architecture and function. Biologists are currently producing large amounts of data focused on physical and genetic protein interactions. Physical interactions dictate the architecture of the cell in terms of how direct associations between molecules constitute protein complexes, while genetic interactions define functional relationships through cause-and-effect relationships between genes. Both of these types of interactions can indicate shared protein functions; however, these two types of interactions are commonly non-overlapping, making their interpretation difficult. Along these lines, it has been noted that genetic interactions commonly occur between members of the same protein complex as well as between functionally related complexes. Here, we present an integrated framework that incorporates both types of interactions to generate large maps of protein complexes as well as highlight connections between related complexes. The ability to rapidly integrate these two types of data in an automated fashion can accelerate the discovery of new members of protein complexes as well as identify functionally related cellular components.
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DOI：
10.1126/science.1135862
发表时间：
2007-02-02
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Driscoll R;Hudson A;Jackson SP
通讯作者：
Jackson SP
斯坦福微阵列数据库：新分析工具的实现和软件的开源发布。
影响因子：
14.9
作者：
Demeter, Janos;Beauheim, Catherine;Gollub, Jeremy;Hernandez-Boussard, Tina;Jin, Heng;Maier, Donald;Matese, John C.;Nitzberg, Michael;Wymore, Farrell;Zachariah, Zachariah K.;Brown, Patrick O.;Sherlock, Gavin;Ball, Catherine A.
通讯作者：
Ball, Catherine A.
影响因子：
14.9
作者：
Güldener U;Münsterkötter M;Oesterheld M;Pagel P;Ruepp A;Mewes HW;Stümpflen V
通讯作者：
Stümpflen V
影响因子：
46.9
作者：
Berger, Michael F.;Philippakis, Anthony A.;Bulyk, Martha L.
通讯作者：
Bulyk, Martha L.
影响因子：
16
作者：
Otero, G;Fellows, J;Svejstrup, JQ
通讯作者：
Svejstrup, JQ